Project Summary Substance use disorders are increasingly described as highly heritable and brain-based. Preclinical work has established that deviations in subcortical and frontal networks are associated with progression from experimentation to use to compulsive drug-seeking, to cycles of abstinence and relapse. Current models emphasize the importance of genetic vulnerabilities to intermediate phenotypes that predispose to substance use and dependence, including neural mechanisms of behavioral disinhibition, reward valuation, negative reinforcement, and negative affect that exacerbates withdrawal/craving. These models also emphasize how such mechanisms might be differentially impacted as a function of neurodevelopment. These various mechanisms, their neural correlates and genetic underpinnings, are increasingly being investigated in the context of large consortium efforts using novel technologies such as the ABCD study, various arms of the Human Connectome Project, TOPMed, AllofUS, and the UK Biobank, to name a few. However, today?s students are not necessarily prepared to leverage these resources to advance the field. We propose a mixed predoctoral/postdoctoral training program, with a central focus on neurobehavioral measures (e.g., neuroimaging), genetically informative designs, and cutting edge quantitative methods to uncover and characterize neurobehavioral mechanisms in the development of addiction. The University of Minnesota is a leader in the investigation of behavioral and molecular genetics of addiction, neurobehavioral mechanisms of substance abuse and its development through the use of preclinical, pharmacological, and neuroimaging techniques, and in quantitative modeling. Led by co-PDs Luciana and Vrieze and with the goal of producing the next generation of scientific/academic leaders, the proposed training program will train six predoctoral and three postdoctoral students each year in quantitative methods and the genetics and/or neurobehavioral mechanisms of addiction. A diverse group of trainees will be selected using stringent criteria from the pool of graduate students (predoctoral) as well as nationally (postdoctoral). The University of Minnesota?s Department of Psychology will lead this effort, with the support of an interdisciplinary team of 19 mentors in addition to the PDs. Each trainee will be funded for a two-year period, will be co-mentored by scientists with topical as well as quantitative expertise, and will pursue a combination of didactic training, lab- based experiences, workshops, seminars focused on professional development, and training in research ethics. For each trainee, individualized development plans will be developed and reviewed by a Steering Committee with articulated milestones related to training in specific research methods and the dissemination of findings. Accordingly, the proposed program will uniquely advance addiction science through its emphasis on computational/quantitative modeling of genetic and neurobehavioral factors relevant to addiction.